Differential effects of interleukin-1 alpha and beta on interleukin-6 and chemokine synthesis in neurones

Interleukin (IL)-1 is a key mediator of neuroinflammation via actions of two agonists IL-1α and β that bind to the IL-1 type I receptor (IL-1RI), and are thought to trigger identical responses. However, evidence suggests that IL-1α and β may have differential actions in the central nervous system (C...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2008-06, Vol.38 (2), p.259-265
Main Authors: Tsakiri, Niki, Kimber, Ian, Rothwell, Nancy J., Pinteaux, Emmanuel
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cerebral Cortex - cytology
Chemokine CCL2 - genetics
Chemokine CCL2 - metabolism
Chemokine CXCL1 - genetics
Chemokine CXCL1 - metabolism
Chemokine CXCL10 - genetics
Chemokine CXCL10 - metabolism
Gene Expression - drug effects
Gene Expression - immunology
Interleukin-1alpha - metabolism
Interleukin-1alpha - pharmacology
Interleukin-1beta - metabolism
Interleukin-1beta - pharmacology
Interleukin-6 - genetics
Interleukin-6 - metabolism
Mice
Mice, Inbred C57BL
Neuroimmunomodulation - physiology
Neurons - cytology
Neurons - immunology
Neurons - metabolism
RNA, Messenger - metabolism
Signal Transduction - drug effects
Signal Transduction - immunology
Sphingomyelin Phosphodiesterase - metabolism
src-Family Kinases - metabolism
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Summary:Interleukin (IL)-1 is a key mediator of neuroinflammation via actions of two agonists IL-1α and β that bind to the IL-1 type I receptor (IL-1RI), and are thought to trigger identical responses. However, evidence suggests that IL-1α and β may have differential actions in the central nervous system (CNS). The objective of this study was to test the hypothesis that IL-1α and β differentially regulate the expression of IL-6 and chemokines KC, IP-10 and MCP-1 in primary neurones. Here we demonstrate that, whilst IL-1β induced significant synthesis of IL-6 in neurones, IL-1α had no effect. In contrast, IL-1α and β induced strong synthesis and constitutive release of chemokines KC, IP-10 and MCP-1 from neurones, and these responses were IL-1RI-dependent. Whilst IL-1β-induced IL-6 synthesis was dependent on the nSMase/Src kinase signalling cascade, specific inhibitors of nSMase (3-OMS) and Src kinase (PP2) failed to inhibit IL-1α- and IL-1β-induced chemokines synthesis, suggesting the existence of alternative signalling pathway(s) in neurones.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2008.02.015